The objective of this proposal is to determine whether chronic, sublethal exposure of rats to carbamate and organophosphate cholinesterase inhibitors, commonly used as insecticides, significantly alters biochemical, physiological, histological or pharmacological parameters of the nervous system. Neuronal mechanisms including neurotransmitter synthesis, release, hydrolysis and receptor interaction will be studied in both the brain and at the neuromuscular junction. The development of skeletal muscle fiber necrosis will be investigated and correlated with biochemical and physiological alterations. If evidence of adaptation to chronic cholinesterase inhibition is present, the significance of the mechanisms involved in this phenomenon will be elucidated. It is hoped that these studies will provide a basis for understanding the potential hazards of the use of these compounds which will enable us to more accurately assess the benefits versus the risks of these agents to human health.